Acquired factor V inhibitor in a context of sepsis and disseminated intravascular coagulation

International audienc

Peningkatkan Ketrampilan Menggunakan Media Pianika dengan Metode Driil SMP 1 Teriak Bengkayang

The purpose of this research is to study the art of music is expected to improve students' skills in using media pianika. The method used in this research is descriptive, with a qualitative approach. Pennelitian shape is action research (action research) with action research procedures including planning, implementation, observation and reflection. Driil method is something to do the same activity over and over again in earnest with the aim to strengthen the skills to be a permanent thing.Learning outcomes in this study is the knowledge and abilities of learners. The conclusions of this study is the use driil method can improve skills in using media pianika seventh grade students of SMP Negeri 1 Shouts Bengkayang. Improved learning outcomes in mind of the average value of student learning outcomes during the first cycle that is 66.28 students' skills in using media pianika musical instruments have not been successful because the average value of students under the KKM is 70. In the second cycle increased to 77, 87 in both categories

Network insights on oxaliplatin anti-cancer mechanisms

Abstract Oxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non-targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum-protein adducts (Pt-Protein) far outnumber Pt-DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin’s function in interrupting DNA-replication was confirmed, but also its role in initiating or intensifying tumorigenesis pathways was uncovered. From our data we present a novel picture of competing signaling networks that collectively provide a plausible explanation of chemotherapeutic resistance, cancer stem cell survival, as well as invasiveness and metastases. Here we highlight oxaliplatin signaling networks, their significance and the clinical implications of these interactions that verifies the importance of network modeling in rational drug design

Compared effects of inhibition and exogenous administration of hydrogen sulphide in ischaemia-reperfusion injury

INTRODUCTION: Haemorrhagic shock is associated with an inflammatory response consecutive to ischaemia-reperfusion (I/R) that leads to cardiovascular failure and organ injury. The role of and the timing of administration of hydrogen sulphide (H2S) remain uncertain. Vascular effects of H2S are mainly mediated through K+ATP-channel activation. Herein, we compared the effects of D,L-propargylglycine (PAG), an inhibitor of H2S production, as well as sodium hydrosulphide (NaHS), an H2S donor, on haemodynamics, vascular reactivity and cellular pathways in a rat model of I/R. We also compared the haemodynamic effects of NaHS administered before and 10 minutes after reperfusion. METHODS: Mechanically ventilated and instrumented rats were bled during 60 minutes in order to maintain mean arterial pressure at 40 +/- 2 mmHg. Ten minutes prior to retransfusion, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl) or PAG (50 mg/kg). PNU, a pore-forming receptor inhibitor of K+ATP channels, was used to assess the role of K+ATP channels. RESULTS: Shock and I/R induced a decrease in mean arterial pressure, lactic acidosis and ex vivo vascular hyporeactivity, which were attenuated by NaHS administered before reperfusion and PNU but not by PAG and NaHS administered 10 minutes after reperfusion. NaHS also prevented aortic inducible nitric oxide synthase expression and nitric oxide production while increasing Akt and endothelial nitric oxide synthase phosphorylation. NaHS reduced JNK activity and p-P38/P38 activation, suggesting a decrease in endothelial cell activation without variation in ERK phosphorylation. PNU + NaHS increased mean arterial pressure when compared with NaHS or PNU alone, suggesting a dual effect of NaHS on vascular reactivity. CONCLUSION: NaHS when given before reperfusion protects against the effects of haemorrhage-induced I/R by acting primarily through a decrease in both proinflammatory cytokines and inducible nitric oxide synthase expression and an upregulation of the Akt/endothelial nitric oxide synthase pathway

Systems analysis reveals a transcriptional reversal of the mesenchymal phenotype induced by SNAIL-inhibitor GN-25

Abstract Background HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models. Results GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression using microarrays from GN-25 treated Kras-HMLE-SNAIL cells showed an orchestrated global re-organization of EMT network genes. The expression signatures were validated at the protein level (down-regulation of mesenchymal markers such as TWIST1 and TWIST2 that was concurrent with up-regulation of epithelial marker E-Cadherin), and RNAi studies validated SNAIL dependent mechanism of action of the drug. Most importantly, GN-25 modulated many major transcription factors (TFs) such as inhibition of oncogenic TFs Myc, TBX2, NR3C1 and led to enhancement in the expression of tumor suppressor TFs such as SMAD7, DD1T3, CEBPA, HOXA5, TFEB, IRF1, IRF7 and XBP1, resulting in MET as well as cell death. Conclusions Our systems and network investigations provide convincing pre-clinical evidence in support of the clinical application of GN-25 for the reversal of EMT and thereby reducing cancer cell aggressiveness

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Penerapan Modifikasi Model Pembelajaran Team Share Tournamet terhadap Kemampuan Komunikasi Siswa Terintegrasi Ada Pappaseng Bugis Makassar

Abstract: Communication skills are very important to be mastered by students in facing the 21st century. It can help and facilitate students to express ideas, and exchange information both verbally and non-verbally. The purpose of this study was to determine the improvement of high school students' communication skills by applying the team share tournament learning model to the material of majas which has local wisdom, namely Pappaseng Bugis Makassar. This type of research is descriptive quantitative which aims to describe systematically the students' communication skills. The sampling technique used purposive sampling and selected students of class XI at one of the public high schools in Bone Regency with a total of 30 students. The instruments used in the study included tests of students' communication skills which were then analyzed using descriptive statistics. The results showed that the communication skills of high school students on figurative language material (folklore) had increased in each indicator after the integration of Makassar Bugis Pappaseng was applied in the learning process. The increase that occurred reached a percentage of up to 89% which was at high.Abstrak: Kemampuan komunikasi merupakan hal yang sangat penting dikuasai oleh siswa dalam menghadapi abad ke-21 karena dapat membantu dan memfasilitasi siswa untuk mengutarakan gagasan, serta bertukar informasi baik secara verbal maupun nonverbal. Tujuan penelitian ini adalah untuk mengetahui peningkatan kemampuan komunikasi siswa SMA dengan penerapan model pembelajaran team share tournament pada materi majas yang dikaitkan dengan kearifan lokal ada pappaseng bugis makassar. Jenis penelitian ini adalah deskriptif kuantitatif yang bertujuan untuk menggambarkan secara sistematis mengenai kemampuan komunikasi siswa. Teknik penentuan sampel digunakan purposive sampling dan dipilih siswa kelas XI pada salah satu SMA Negeri yang terdapat di Kabupaten Bone dengan jumlah 30 siswa. Instrumen yang digunakan dalam penelitian meliputi tes kemampuan komunikasi siswa yang selanjutnya dianalisis menggunakan statistik deskriptif. Hasil penelitian menunjukkan bahwa kemampuan komunikasi siswa SMA pada materi majas (cerita rakyat) mengalami peningkatan pada setiap indikatornya setelah diterapkan integrasi ada pappaseng Bugis Makassar dalam proses pembelajaran. Peningkatan yang terjadi mencapai persentase hingga 89% yang berada pada kategori tinggi

Target blood pressure for septic and vasodilatory shock: what is optimal?

International audienc